Search

Objective To determine the prevalence of stress hyperglycaemia in people presenting with acute coronary syndrome (ACS), and the relationships between admission glucose and cardiac damage, cardiovascular mortality and morbidity. Methods In a prospective observational study people presenting with ACS at the Gold Coast Hospital had their admission glucose (AG) level tested to determine stress hyperglycaemia. A range of measurements supplemented this data including troponin levels, category of ACS and major adverse coronary events (MACEs) were obtained through hospital records and patient follow-up post-discharge. Results One hundred eighty-eight participants were recruited. The prevalence of stress hyperglycaemia in ACS was 44% with 31% having a previous diagnosis of type 2 diabetes and 7.7% had undiagnosed diabetes. The stress hyperglycaemic group had a significantly higher median troponin levels compared to participants with normal blood glucose levels on admission (p < 0.05) however the highest presenting glucose group (> 15 mmol/L) had troponin levels similar to people presenting with normal blood glucose levels and ACS (p > 0.05). Conclusions Cardiac necrosis as measured by troponin levels is significantly increased in people with ACS and stress hyperglycaemia. This study found that one in four participants presenting with ACS and an admission glucose of > 7.0 had no previous diagnosis for diabetes. Practice implication Consistently ordering HbA1C testing on patients with high AG can enable earlier diagnosis and treatment of diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Development of urinary incontinence, for many women, occurs following menopause. Dietary phytoestrogens consumed over the long term may affect the contractile function and maintenance of the urinary bladder in post menopausal women. This study examined the muscarinic receptor mediated contractile responses in the rat isolated bladder in response to ovariectomy and long term dietary phytoestrogen consumption. Main methods: Ovariectomised or sham-operated female Wistar rats (8weeks) were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. Bladders were dissected from rats at 12, 24 and 52weeks of age and placed in 25ml organ baths filled with McEwans solution. Key findings: The contractile response to carbachol, in 12week old female rats did not change as a result of dietary phytoestrogens or ovariectomy (P>0.05). At 24weeks of age, detrusor muscle strip responses to carbachol from non-soy fed ovariectomised rats were attenuated (P<0.05). At 52weeks, bladder detrusor strip responses to carbachol were reduced in all treatment groups with the exception of the soy-fed sham operated rats. Significance: These results suggest an age-related reduction in the contractile response of the detrusor to the muscarinic receptor agonist carbachol, which may be prevented by long term dietary phytoestrogen intake. [Copyright &y& Elsevier]

1. The effect of the adenosine A2 receptor (AdoA2R) agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) on adenosine A1 receptor (AdoA1R)-mediated negative inotropic responses was investigated in rat heart. 2. Hearts from male Wistar rats (250–350 g) were perfused with Krebs’–Henseleit solution at constant flow in non-recirculating Langendorff mode. Hearts were paced at 5 Hz (5 ms duration, supramaximal voltage) via ventricular electrodes. After 30 min equilibration, (R)-N6-phenylisopropyl adenosine (R-PIA) concentration–response curves were constructed in the absence or presence of DPMA. 3. In paced hearts, R-PIA induced concentration-dependent decreases in triple product (heart rate × peak systolic developed pressure × d P / d tmax), which were significantly attenuated by 1 nmol / L DPMA with a shift in pEC50 from 8.0 ± 0.5 ( n = 9) in control hearts to 6.63 ± 1.03 ( n = 5) in treated tissues ( P < 0.05). The AdoA2AR antagonist 8-(3-chlorostyryl)caffeine (1 μmol / L) and the adenylyl cyclase inhibitor cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL12330A; 100 nmol / L) reversed the effects of DPMA on AdoA1R-mediated negative inotropic actions, whereas the AdoA2BR antagonist alloxazine (3 μmol / L) had no effect on DPMA activity. 4. The results of the present study show that stimulation of the AdoA2R attenuates AdoA1R-dependent reductions in inotropic state. The receptor involved appears to be the AdoA2AR and its action involves stimulation of adenylyl cyclase activity. [ABSTRACT FROM AUTHOR]

l-Arginine increases myocardial nitric oxide production. Nitric oxide mediates many of the cardiovascular actions of adenosine and modulates adenosine metabolism. In this study, we examined the effect of chronicl-arginine (5%) intake on cardiac nitric oxide synthase (NOS) and adenosine receptor expression and cardiac function in rat Langendorff-isolated perfused hearts. Our results show that 4-week chronicl-arginine ingestion increases the weight of rat hearts by 17.6% (P < 0.05).l-Arginine treatment decreased the expression of all the cardiac adenosine receptors, with reductions in adenosine A1 (20-fold), A2A (7.7-fold), A2B (76-fold) and A3 (25.6-fold) mRNA (P < 0.05). NOS expression was variably affected with no change in the expression of NOS1 and 4.2-fold down-regulation of NOS3 expression with chronicl-arginine treatment (P < 0.05). NOS2 was expressed in control tissues; however, inl-arginine-treated hearts the amount of NOS2 mRNA was reduced to non-detectable levels. Following chronicl-arginine treatment, an increase in coronary perfusion pressure was observed (P < 0.05). Purine efflux was used as an indicator of metabolic efficiency.l-Arginine did not alter catecholamine-induced purine efflux (P > 0.05); however, noradrenaline-mediated increases in contractility and myocardial oxygen consumption were reduced. Vasodilator responses to 5′-N-ethylcarboxamidoadenosine (NECA) were reduced in hearts froml-arginine-treated rats and the NOS inhibitor Nϖ-nitro-l-arginine methyl ester (3 µM) did not inhibit responses to NECA. In conclusion, 4-week dietary supplementation ofl-arginine reduced the expression of cardiac adenosine receptors and NOSs with a subsequent decrease in noradrenaline-stimulated cardiac function and adenosine receptor-mediated coronary vasodilation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the effects of age on adenosine A1 receptor (ADORA1) mediated vascular, inotropic and chronotropic functional responses in isolated rat hearts. Methods: NECA (5′-(N-ethylcarboxamido)adenosine) and R-PIA (R-N 6-(1-methyl-2-phenylethyl)adenosine) concentration–response curves were produced in Langendorff prepared hearts isolated from immature (6 weeks), young (16 weeks) and mature (52 weeks) male Wistar rats and the effects of DPCPX (ADORA1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine, 30 nM) and pertussis toxin pre-treatment (PTX, 48 h, 10 μg/kg IP, inhibits Gi/o-protein) were observed. Results: NECA mediated coronary vasodilation and induced biphasic concentration–response curves in hearts from immature rats (pEC50 8.5 (8.1–8.9) and 11.3 (10.3–12.3)). At the low sensitivity site, the potency of NECA increased in young but not mature rats and remained unchanged at the high sensitivity site. Both DPCPX and PTX each blocked NECA at the high sensitivity site in immature rats, producing monophasic concentration–response curves (pEC50 8.6 (8.5–9.9) for DPCPX and pEC50 8.7 (8.3–9.0) for PTX), but not in young and mature rats. A vasoconstrictor response was observed at low NECA concentrations in hearts from PTX pre-treated immature rats, but not in hearts from young and mature rats, and the response was inhibited by DPCPX. No age related changes were observed in R-PIA mediated negative inotropic and chronotropic responses (P >0.05). Conclusion: ADORA1 mediates a vasodilator response as well as a vasoconstrictor response in the coronary resistance vessels; the latter occurs via a PTX-insensitive pathway and declines with age. [Copyright &y& Elsevier]

In our laboratory we have developed a quantitative-polymerase chain reaction (Q-PCR) strategy to examine the differential expression of adenosine receptor (ADOR), A1, A2A, A2B and A3, and estrogen receptors (ER) α and β. Brain and uterine mRNA were first used to optimise specific amplification conditions prior to SYBR Green I real time analysis of receptor subtype expression. SYBR Green I provided a convenient and sensitive means of examining specific PCR amplification product in real time, and allowed the generation of standard curves from which relative receptor abundance could be determined. Real time Q-PCR analysis was then performed, to examine changes in receptor expression levels in brains of adult female Wistar rats 3-month post ovariectomy. Comparison with sham-operated age-matched control rats demonstrated both comparative and absolute-copy number changes in receptor levels. Evaluation of both analytical methods investigated 18S rRNA as an internal reference for comparative gene expression analysis in the brain. The results of this study revealed preferential repression of ADORA2A (>4-fold down) and consistent (>2-fold) down-regulation of ADORA1, ADORA3, and ER-β, following ovariectomy. No change was found in ADORA2B or ER-α. Analysis of absolute copy number in this study revealed a correlation between receptor expression in response to ovariectomy, and relative receptor subtype abundance in the brain. [Copyright &y& Elsevier]

Presents information on a study which investigated the role of adenosine in the mediation of coronary and aortic smooth muscle dilation, and the effect of age on the process. Methodology; Results of the study; Discussion.

Examines the effect of acute and chronic caffeine on the response to ischemia-reperfusion in rat isolated perfused hearts. Absence of effects of acute nor chronic caffeine on normoxic heart rate; Decrease coronary flow with acute caffeine; Inhibition of left ventricular diastolic pressure recovery by acute caffeine.

Characterizes age-related changes in direct A1-mediated bradycardia. Changes in functional sensitivity to adenosine as caused by changes at the level of the A1 receptor itself and/or changes in adenosine transport and metabolism; Physiological significance in the older heart of increased functional sensitivity to adenosine.

Provides information on a study which analyzed the impact of age on functional sensitivity to A...-adenosine receptor activation in rats. Methods of the study; Results and discussion.

Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth. [ABSTRACT FROM AUTHOR]

Background: Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods: mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results: Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions: This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. [ABSTRACT FROM AUTHOR]

Abstract: Intra- and extracellular adenosine levels rise in response to physiological stimuli and with metabolic/energetic perturbations, inflammatory challenge and tissue injury. Extracellular adenosine engages members of the G-protein coupled adenosine receptor (AR) family to mediate generally beneficial acute and adaptive responses within all constituent cells of the heart. In this way the four AR sub-types—A1, A2A, A2B, and A3Rs—regulate myocardial contraction, heart rate and conduction, adrenergic control, coronary vascular tone, cardiac and vascular growth, inflammatory–vascular cell interactions, and cellular stress-resistance, injury and death. The AR sub-types exert both distinct and overlapping effects, and may interact in mediating these cardiovascular responses. The roles of the ARs in beneficial modulation of cardiac and vascular function, growth and stress-resistance render them attractive therapeutic targets. However, interactions between ARs and with other receptors, and their ubiquitous distribution throughout the body, can pose a challenge to the implementation of site- and target-specific AR based pharmacotherapy. This review outlines cardiovascular control by adenosine and the AR family in health and disease, including interactions between AR sub-types within the heart and vessels. [Copyright &y& Elsevier]

The effect of an allosteric modulator of the adenosine A1 receptors was investigated using an ischaemia-reperfusion protocol in murine isolated hearts. Isolated hearts were perfused with Kreb-Henseleit solution gassed with carbogen gas (95% O2 and 5% CO2) in Langendorff mode and electrically paced at 480 bpm. Following 20 min equilibration and 20 min global normothermic ischaemia, the allosteric modulator VCP333 (1 μM) or the adenosine A1 receptor partial agonist VCP102 (10 μM) were infused after 5 min of reperfusion for 15 min. Upon termination of the drug treatment, reperfusion continued for a further 40 min. At the end of 60 min reperfusion, treatment with VCP333 or VCP102 improved the recovery of the left ventricular developed pressure when compared to control group responses (p < 0.05). Neither compound affected end diastolic pressure, coronary flow rates or dP/dtmax values when compared to control tissues during reperfusion (p > 0.05). The infusion of VCP102 or VCP333 during reperfusion reduced cardiac troponin I efflux to 6.7% and 25% respectively of control heart efflux (p < 0.05). This data indicates that the allosteric modulator of the adenosine A1 receptor (VCP333) has similar characteristics to the adenosine receptor partial agonist VCP102 as it improves cardiac function and reduces myocardial cell death following an ischaemic episode. [ABSTRACT FROM AUTHOR]